{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:02:02Z","timestamp":1787724122500,"version":"build-2784847793"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:p>It is known that co\u2010administration of CYP3A inducers may decrease the effectiveness of oral contraceptives containing progestins as mono\u2010preparations or combined with ethinylestradiol. In a randomized clinical drug\u2010drug interaction study, we investigated the effects of CYP3A induction on the pharmacokinetics of commonly used progestins and ethinylestradiol. Rifampicin was used to induce CYP3A. The progestins chosen as victim drugs were levonorgestrel, norethindrone, desogestrel, and dienogest as mono\u2010products, and drospirenone combined with ethinylestradiol. Postmenopausal women (<jats:italic>n<\/jats:italic>\u00a0=\u00a012\u201314 per treatment group) received, in fixed sequence, a single dose of the victim drug plus midazolam without rifampicin, with rifampicin 10\u00a0mg\/day (weak induction), and with rifampicin 600\u00a0mg\/day (strong induction). The effects on progestin exposure were compared with the effects on midazolam exposure (as a benchmark). Unbound concentrations were evaluated for drugs binding to sex hormone binding globulin. Weak CYP3A induction, as confirmed by a mean decrease in midazolam exposure by 46%, resulted in minor changes in progestin exposure (mean decreases: 15\u201337%). Strong CYP3A induction, in contrast, resulted in mean decreases by 57\u201390% (mean decrease in midazolam exposure: 86%). Namely, the magnitude of the observed induction effects varied from weak to strong. Our data might provide an impetus to revisit the currently applied clinical recommendations for oral contraceptives, especially for levonorgestrel and norethindrone\u2010containing products, and they might give an indication as to which progestin could be used, if requested, by women taking weak CYP3A inducers\u2014although it is acknowledged that the exact exposure\u2010response relationship for contraceptive efficacy is currently unclear for most progestins.<\/jats:p>","DOI":"10.1002\/cpt.1848","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T17:45:18Z","timestamp":1586540718000},"page":"798-807","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Effects of Weak and Strong CYP3A Induction by Rifampicin on the Pharmacokinetics of Five Progestins and Ethinylestradiol Compared to Midazolam"],"prefix":"10.1111","volume":"108","author":[{"given":"Herbert","family":"Wiesinger","sequence":"first","affiliation":[{"name":"Bayer AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Klein","sequence":"additional","affiliation":[{"name":"Bayer AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Rottmann","sequence":"additional","affiliation":[{"name":"Bayer AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Nowotny","sequence":"additional","affiliation":[{"name":"Bayer AG Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Riecke","sequence":"additional","affiliation":[{"name":"Bayer AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Gashaw","sequence":"additional","affiliation":[{"name":"Bayer AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarete","family":"Brudny\u2010Kl\u00f6ppel","sequence":"additional","affiliation":[{"name":"Bayer AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Fricke","sequence":"additional","affiliation":[{"name":"Bayer AG Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"H\u00f6chel","sequence":"additional","affiliation":[{"name":"Bayer AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Bayer AG Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2011.01.021"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12499"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1285"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.087270"},{"key":"e_1_2_10_5_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER).Labeling for combined hormonal contraceptives \u2010 Guidance for industry. 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